tbuckley/cabot-search huggingface dataset:
Disease-specific protein corona formed in pathological intestine enhances the oral absorption of nanoparticles
Authors: Jiawei Wu, Liyun Xing, Yaxian Zheng, Yinglan Yu, Ruinan Wu, Xi Liu, Lian Li, Yuan Huang
Journal: Acta Pharmaceutica Sinica B (2023)

Protein corona (PC) has been identified to impede the transportation of intravenously injected nanoparticles (NPs) from blood circulation to their targeted sites. However, how intestinal PC (IPC) affects the delivery of orally administered NPs are still needed to be elucidated. Here, we found that IPC exerted "positive effect" or "negative effect" depending on different pathological conditions in the gastrointestinal tract. We prepared polystyrene nanoparticles (PS) adsorbed with different IPC derived from the intestinal tract of healthy, diabetic, and colitis rats (H-IPC@PS, D-IPC@PS, C-IPC@PS). Proteomics analysis revealed that, compared with healthy IPC, the two disease-specific IPC consisted of a higher proportion of proteins that were closely correlated with transepithelial transport across the intestine. Consequently, both D-IPC@PS and C-IPC@PS mainly exploited the recycling endosome and ER-Golgi mediated secretory routes for intracellular trafficking, which increased the transcytosis from the epithelium. Together, disease-specific IPC endowed NPs with higher intestinal absorption. D-IPC@PS posed "positive effect" on intestinal absorption into blood circulation for diabetic therapy. Conversely, C-IPC@PS had "negative effect" on colitis treatment because of unfavorable absorption in the intestine before arriving colon. These results imply that different or even opposite strategies to modulate the disease-specific IPC need to be adopted for oral nanomedicine in the treatment of variable diseases.
Amelioration of ethanol-induced oxidative stress and alcoholic liver disease by in vivo RNAi targeting Cyp2e1
Authors: Yalan Wang, Qiubing Chen, Shuang Wu, Xinyu Sun, Runting Yin, Zhen Ouyang, Hao Yin, Yuan Wei
Journal: Acta Pharmaceutica Sinica B (2023)

Alcoholic liver disease (ALD) results from continuous and heavy alcohol consumption. The current treatment strategy for ALD is based on alcohol withdrawal coupled with antioxidant drug intervention, which is a long process with poor efficacy and low patient compliance. Alcohol-induced CYP2E1 upregulation has been demonstrated as a key regulator of ALD, but CYP2E1 knockdown in humans was impractical, and pharmacological inhibition of CYP2E1 by a clinically relevant approach for treating ALD was not shown. In this study, we developed a RNAi therapeutics delivered by lipid nanoparticle, and treated mice fed on Lieber-DeCarli ethanol liquid diet weekly for up to 12 weeks. This RNAi-based inhibition of Cyp2e1 expression reduced reactive oxygen species and oxidative stress in mouse livers, and contributed to improved ALD symptoms in mice. The liver fat accumulation, hepatocyte inflammation, and fibrosis were reduced in ALD models. Therefore, this study suggested the feasibility of RNAi targeting to CYP2E1 as a potential therapeutic tool to the development of ALD.
Erratum to “European Association of Urology (EAU) Prognostic Factor Risk Groups for Non–muscle-invasive Bladder Cancer (NMIBC) Incorporating the WHO 2004/2016 and WHO 1973 Classification Systems for Grade: An Update from the EAU NMIBC Guidelines Panel” [Eur. Urol. 79(4) (2021) 480–488]
Authors: Richard J. Sylvester, Oscar Rodríguez, Virginia Hernández, Diana Turturica, Lenka Bauerová, Harman Max Bruins, Johannes Bründl, Theo H. van der Kwast, Antonin Brisuda, José Rubio-Briones, Maximilian Seles, Anouk E. Hentschel, Venkata R.M. Kusuma, Nicolai Huebner, Juliette Cotte, Laura S. Mertens, Dimitrios Volanis, Olivier Cussenot, Jose D. Subiela Henríquez, Enrique de la Peña, Francesca Pisano, Michael Pešl, Antoine G. van der Heijden, Sonja Herdegen, Alexandre R. Zlotta, Jaromir Hacek, Ana Calatrava, Sebastian Mannweiler, Judith Bosschieter, David Ashabere, Andrea Haitel, Jean-François Côté, Soha El Sheikh, Luca Lunelli, Ferran Algaba, Isabel Alemany, Francesco Soria, Willemien Runneboom, Johannes Breyer, Jakko A. Nieuwenhuijzen, Carlos Llorente, Luca Molinaro, Christina A. Hulsbergen-van de Kaa, Matthias Evert, Lambertus A.L.M. Kiemeney, James N'Dow, Karin Plass, Otakar Čapoun, Viktor Soukup, Jose L. Dominguez-Escrig, Daniel Cohen, Joan Palou, Paolo Gontero, Maximilian Burger, Richard Zigeuner, Amir Hugh Mostafid, Shahrokh F. Shariat, Morgan Rouprêt, Eva M. Compérat, Marko Babjuk, Bas W.G. van Rhijn
Journal: European Urology (2023)
Inherited and acquired errors of type I interferon immunity govern susceptibility to COVID-19 and multisystem inflammatory syndrome in children
Authors: Giorgia Bucciol, Isabelle Meyts, Laurent Abel, Salah Al-Muhsen, Alessandro Aiuti, Fahd Al-Mulla, Evangelos Andreakos, Novelli Antonio, Andrés A. Arias, Sophie Trouillet-Assant, Alexandre Belot, Catherine M. Biggs, Ahmed A. Bousfiha, Alex Bolze, Alessandro Borghesi, Petter Brodin, John Christodoulou, Aurélie Cobat, Antonio Condino-Neto, Stefan Constantinescu, Clifton L. Dalgard, Sara Espinosa-Padilla, Jacques Fellay, Carlos Flores, José Luis Franco, Antoine Froidure, Guy Gorochov, Filomeen Haerynck, Rabih Halwani, Elena W.Y. Hsieh, Yuval Itan, Kai Kisand, Yu-Lung Lau, Davood Mansouri, Isabelle Meyts, Trine H. Mogensen, Lisa F.P. Ng, Luigi D. Notarangelo, Giuseppe Novelli, Satoshi Okada, Tayfun Ozcelik, Rebeca Perez de Diego, Carolina Prando, Aurora Pujol, Lluis Quintana-Murci, Laurent Renia, Igor Resnick, Lucie Roussel, Carlos Rodríguez-Gallego, Vanessa Sancho-Shimizu, Mohammed Shahrooei, Pere Soler-Palacín, András N. Spaan, Ivan Tancevski, Stuart G. Tangye, Ahmad Abou Tayoun, Şehime Gülsün Temel, Pierre Tiberghien, Jordi Perez Tur, Stuart E. Turvey, Furkan Uddin, Mohammed J. Uddin, Mateus Vidigal, Donald C. Vinh, Mayana Zatz, Keisuke Okamoto, David S. Perlin, Graziano Pesole, Christian Thorball, Diederik van de Beek, Roger Colobran, Joost Wauters, Shen-Ying Zhang, Qian Zhang, Helen C. Su, Jean-Laurent Casanova
Journal: Journal of Allergy and Clinical Immunology (2023)

Since the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/coronavirus disease 2019 (COVID-19) pandemic, global sequencing efforts have led in the field of inborn errors of immunity, and inspired particularly by previous research on life-threatening influenza, they have revealed that known and novel inborn errors affecting type I interferon immunity underlie critical COVID-19 in up to 5% of cases. In addition, neutralizing autoantibodies against type I interferons have been identified in up to 20% of patients with critical COVID-19 who are older than 80 years and 20% of fatal cases, with a higher prevalence in men and individuals older than 70 years. Also, inborn errors impairing regulation of type I interferon responses and RNA degradation have been found as causes of multisystem inflammatory syndrome in children, a life-threatening hyperinflammatory condition complicating otherwise mild initial SARS-CoV-2 infection in children and young adults. Better understanding of these immunologic mechanisms can aid in designing treatments for severe COVID-19, multisystem inflammatory syndrome in children, long COVID, and neuro-COVID.
Good-enough attentional guidance
Authors: Xinger Yu, Zhiheng Zhou, Stefanie I. Becker, Sage E.P. Boettcher, Joy J. Geng
Journal: Trends in Cognitive Sciences (2023)

Theories of attention posit that attentional guidance operates on information held in a target template within memory. The template is often thought to contain veridical target features, akin to a photograph, and to guide attention to objects that match the exact target features. However, recent evidence suggests that attentional guidance is highly flexible and often guided by non-veridical features, a subset of features, or only associated features. We integrate these findings and propose that attentional guidance maximizes search efficiency based on a 'good-enough' principle to rapidly localize candidate target objects. Candidates are then serially interrogated to make target-match decisions using more precise information. We suggest that good-enough guidance optimizes the speed-accuracy-effort trade-offs inherent in each stage of visual search.
NRF2 activation induces NADH-reductive stress, providing a metabolic vulnerability in lung cancer
Authors: Tommy Weiss-Sadan, Maolin Ge, Makiko Hayashi, Magdy Gohar, Cong-Hui Yao, Adriaan de Groot, Stefan Harry, Alexander Carlin, Hannah Fischer, Lei Shi, Ting-Yu Wei, Charles H. Adelmann, Konstantin Wolf, Tristan Vornbäumen, Benedikt R. Dürr, Mariko Takahashi, Marianne Richter, Junbing Zhang, Tzu-Yi Yang, Vindhya Vijay, David E. Fisher, Aaron N. Hata, Marcia C. Haigis, Raul Mostoslavsky, Nabeel Bardeesy, Thales Papagiannakopoulos, Liron Bar-Peled
Journal: Cell Metabolism (2023)
Two-year follow-up of patients with post-COVID-19 condition in Sweden: a prospective cohort study
Authors: Carl Wahlgren, Gustaf Forsberg, Anestis Divanoglou, Åse Östholm Balkhed, Katarina Niward, Sören Berg, Richard Levi
Journal: The Lancet Regional Health - Europe (2023)

Few studies have reported the long-term health effects of COVID-19. The regional population-based Linköping COVID-19 study (LinCoS) included all patients hospitalised due to COVID-19 during the first pandemic wave. Four months post-discharge, over 40% (185/433) experienced persisting symptoms and activity/participation limitations, indicating post-COVID-19 condition (PCC). The present follow-up study aimed to determine the long-term recovery among these patients 24 months post-admission. This prospective cohort study included all patients from LinCoS with PCC at four months post-discharge. We repeated the same structured interview at a 24-month follow-up to identify persisting symptoms and their impact on daily life. Intercurrent health issues were identified by reviewing medical records. Of 185 patients with PCC at 4 months post-discharge, 181 were alive at the 24-month assessment and 165 agreed to participate. Of those, 21% (35/165) had been readmitted to hospital for various causes in the interim period. The majority of patients (139/165, 84%) reported persisting problems affecting everyday life at 24 months. Significant improvements were seen in the prevalence and magnitude of some symptoms/limitations compared with four months post-discharge. Cognitive, sensorimotor, and fatigue symptoms were the most common persisting symptoms at 24 months. No clear difference was evident between individuals treated in the intensive care unit (ICU) and non-ICU-treated individuals. Approximately half of those who were on sick leave related to PCC at four months after infection were on sick leave at 24 months. This is one of the first studies to report 2-year outcomes in patients with PCC following COVID-19 hospitalisation. Despite some improvements over time, we found a high prevalence of persisting symptoms and a need for long-term follow-up and rehabilitation post COVID-19 infection. The study was funded by Region Östergötland.
Application of microfluidic technologies on COVID-19 diagnosis and drug discovery
Authors: Zhun Lin, Zhengyu Zou, Zhe Pu, Minhao Wu, Yuanqing Zhang
Journal: Acta Pharmaceutica Sinica B (2023)

The ongoing coronavirus disease 2019 (COVID-19) pandemic has boosted the development of antiviral research. Microfluidic technologies offer powerful platforms for diagnosis and drug discovery for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnosis and drug discovery. In this review, we introduce the structure of SARS-CoV-2 and the basic knowledge of microfluidic design. We discuss the application of microfluidic devices in SARS-CoV-2 diagnosis based on detecting viral nucleic acid, antibodies, and antigens. We highlight the contribution of lab-on-a-chip to manufacturing point-of-care equipment of accurate, sensitive, low-cost, and user-friendly virus-detection devices. We then investigate the efforts in organ-on-a-chip and lipid nanoparticles (LNPs) synthesizing chips in antiviral drug screening and mRNA vaccine preparation. Microfluidic technologies contribute to the ongoing SARS-CoV-2 research efforts and provide tools for future viral outbreaks.
Brief Report: Durvalumab After Chemoradiotherapy in Unresectable Stage III EGFR-Mutant NSCLC: A Post Hoc Subgroup Analysis From PACIFIC
Authors: Jarushka Naidoo, Scott Antonia, Yi-Long Wu, Byoung Chul Cho, Piruntha Thiyagarajah, Helen Mann, Michael Newton, Corinne Faivre-Finn
Journal: Journal of Thoracic Oncology (2023)
Brief Report: Canadian Cancer Trials Group IND.227: A Phase 2 Randomized Study of Pembrolizumab in Patients With Advanced Malignant Pleural Mesothelioma (NCT02784171)
Authors: Maria Carmela Piccirillo, Quincy Chu, Penelope Bradbury, Wei Tu, Courtney H. Coschi, Federica Grosso, Marie Florescu, Manlio Mencoboni, John R. Goffin, Maria Pagano, Fortunato Ciardiello, Fabiana Letizia Cecere, Mark Vincent, Roberto Ferrara, David E. Dawe, Desiree Hao, Christopher W. Lee, Alessandro Morabito, Cesare Gridelli, Luigi Cavanna, Mussawar Iqbal, Normand Blais, Natasha B. Leighl, Paul Wheatley-Price, Ming-Sound Tsao, Francesca Ugo, Hazem El-Osta, Piera Gargiulo, Pierre-Olivier Gaudreau, Dongsheng Tu, Joana Sederias, Pamela Brown-Walker, Francesco Perrone, Lesley Seymour, Scott A. Laurie
Journal: Journal of Thoracic Oncology (2023)
Selective Mediastinal Lymph Node Dissection Strategy for Clinical T1N0 Invasive Lung Cancer: A Prospective, Multicenter, Clinical Trial
Authors: Yang Zhang, Chaoqiang Deng, Qiang Zheng, Bin Qian, Junjie Ma, Chunyang Zhang, Yan Jin, Xuxia Shen, Yibing Zang, Yufeng Guo, Fangqiu Fu, Hang Li, Shanbo Zheng, Haoxuan Wu, Qingyuan Huang, Shengping Wang, Quan Liu, Ting Ye, Yihua Sun, Yawei Zhang, Jiaqing Xiang, Hong Hu, Yuan Li, Haiquan Chen
Journal: Journal of Thoracic Oncology (2023)

We aimed to prospectively evaluate our previously proposed selective mediastinal lymph node (LN) dissection strategy for peripheral clinical T1N0 invasive NSCLC.This is a multicenter, prospective clinical trial in China. We set six criteria for predicting negative LN stations and finally guiding selective LN dissection. Consolidation tumor ratio less than or equal to 0.5, segment location, lepidic-predominant adenocarcinoma (LPA), negative hilar nodes (stations 10-12), and negative visceral pleural invasion (VPI) were used separately or in combination as predictors of negative LN status in the whole, superior, or inferior mediastinal zone. LPA, hilar node involvement, and VPI were diagnosed intraoperatively. All patients actually underwent systematic mediastinal LN dissection. The primary end point was the accuracy of the strategy in predicting LN involvement. If LN metastasis occurred in certain mediastinal zone that was predicted to be negative, it was considered as an "inaccurate" case.A total of 720 patients were enrolled. The median number of LN dissected was 15 (interquartile range: 11-20). All negative node status in certain mediastinal zone was correctly predicted by the strategy. Compared with final pathologic findings, the accuracy of frozen section to diagnose LPA, VPI, and hilar node metastasis was 94.0%, 98.9%, and 99.6%, respectively. Inaccurate intraoperative diagnosis of LPA, VPI, or hilar node metastasis did not lead to inaccurate prediction of node-negative status.This is the first prospective trial validating the specific mediastinal LN metastasis pattern in cT1N0 invasive NSCLC, which provides important evidence for clinical applications of selective LN dissection strategy.
Deep palmar phenotyping in atopic eczema: patterns associated with <i>filaggrin</i> variants, disease severity and barrier function in a South Asian population
Authors: Bjorn R Thomas, Xiang Li Tan, Stefan Van Duijvenboden, Sarah C Hogan, Aaron J Hughes, Soha S Tawfik, Sasha Dhoat, Ravinder Atkar, Elizabeth J Robinson, Syedia R Rahman, Samiha Rahman, Rehana A Ahmed, Rubina Begum, Habiba Khanam, Emma L Bourne, Eva L Wozniak, Charles A Mein, David P Kelsell, Edel A O’Toole
Journal: British Journal of Dermatology (2023)

Hyperlinear palms are described as a feature of loss-of-function (LoF) variants in filaggrin (FLG).To explore the phenotype of participants (age < 31 years) with atopic eczema of Bangladeshi ancestry from East London and investigate which factors best associate with LoF FLG variants.A cross-sectional study with participants recruited between May 2018 and December 2020. Patterns of palmar linearity were categorized and modelled with the Eczema Area and Severity Index (EASI), transepidermal water loss (TEWL), skin hydration (SH) and LoF FLG variants.There were 506 complete cases available. Five palm patterns were noted. The 'prominent diamond' pattern associated best with EASI [marginal effects (ME) 2.53, 95% confidence interval (CI) 1.74-3.67], SH (ME 0.85, 95% CI 0.78-0.96) and TEWL (ME 1.32, 95% CI 1.11-1.62). Using five palm patterns had some ability to discriminate LoF FLG variants [area under the receiver operator characteristic (AUROC) 76.32%, 95% CI 71.91-80.73], improving to 77.99% (73.70-82.28) with the addition of SH. In subgroup analysis with only fine perpendicular/prominent diamond patterns the AUROC was 89.11% (95% CI 84.02-94.19).This was a single-centre study design with humans classifying clinical patterns. The stability of temperature and humidity was not guaranteed across TEWL and SH measurements despite using a climate-controlled room. Palm patterns associate with EASI and TEWL. The fine perpendicular/prominent diamond patterns are markers to detect the absence/presence of LoF FLG variants, respectively.
Clinical, histological, and molecular features of gliomas in adults with neurofibromatosis type 1
Authors: Carlos G Romo, Anna F Piotrowski, Jian L Campian, Jose Diarte, Fausto J Rodriguez, Tejus A Bale, Sonika Dahiya, David H Gutmann, Calixto-Hope G Lucas, Laura Prichett, Ingo Mellinghoff, Jaishri O Blakeley
Journal: Neuro-Oncology (2023)

Abstract Background People with NF1 have an increased prevalence of central nervous system malignancy. However, little is known about the clinical course or pathologic features of NF1-associated gliomas in adults, limiting clinical care and research. Methods Adults (≥18 years) with NF1 and histologically confirmed non-optic pathway gliomas (non-OPGs) at Johns Hopkins Hospital, Memorial Sloan Kettering Cancer Center, and Washington University presenting between 1990 and 2020 were identified. Retrospective data were collated, and pathology was reviewed centrally. Results Forty-five patients, comprising 23 females (51%), met eligibility criteria, with a median of age 37 (18–68 years) and performance status of 80% (30%–100%). Tissue was available for 35 patients. Diagnoses included infiltrating (low-grade) astrocytoma (9), glioblastoma (7), high-grade astrocytoma with piloid features (4), pilocytic astrocytoma (4), high-grade astrocytoma (3), WHO diagnosis not reached (4) and one each of gliosarcoma, ganglioglioma, embryonal tumor, and diffuse midline glioma. Seventy-one percent of tumors were midline and underwent biopsy only. All 27 tumors evaluated were IDH1-wild-type, independent of histology. In the 10 cases with molecular testing, the most common genetic variants were NF1, EGFR, ATRX, CDKN2A/B, TP53, TERT, and MSH2/3 mutation. While the treatments provided varied, the median overall survival was 24 months [2–267 months] across all ages, and 38.5 [18–109] months in individuals with grade 1–2 gliomas. Conclusions Non-OPGs in adults with NF1, including low-grade tumors, often have an aggressive clinical course, indicating a need to better understand the pathobiology of these NF1-associated gliomas.
A Cyclodiaryliodonium NOX Inhibitor for the Treatment of Pancreatic Cancer via Enzyme‐Activatable Targeted Delivery by Sulfated Glycosaminoglycan Derivatives
Authors: Jiadong Pang, Daqian Zhu, Yang Liu, Dingxin Liu, Chunhua Zhao, Jianeng Zhang, Shengping Li, Zexian Liu, Xiaobing Li, Peng Huang, Shijun Wen, Jiang Yang
Journal: Advanced Healthcare Materials (2023)

Pancreatic cancer renders a principal cause of cancer mortalities with a dismal prognosis, lacking sufficiently safe and effective therapeutics. Here, diversified cyclodiaryliodonium (CDAI) NADPH oxidase (NOX) inhibitors are rationally designed with tens of nanomolar optimal growth inhibition, and CD44-targeted delivery is implemented using synthesized sulfated glycosaminoglycan derivatives. The self-assembled nanoparticle-drug conjugate (NDC) enables hyaluronidase-activatable controlled release and facilitates cellular trafficking. NOX inhibition reprograms the metabolic phenotype by simultaneously impairing mitochondrial respiration and glycolysis. Moreover, the NDC selectively diminishes non-mitochondrial reactive oxygen species (ROS) but significantly elevates cytotoxic ROS through mitochondrial membrane depolarization. Transcriptomic profiling reveals perturbed p53, NF-κB, and GnRH signaling pathways interconnected with NOX inhibition. After being validated in patient-derived pancreatic cancer cells, the anticancer efficacy is further verified in xenograft mice bearing heterotopic and orthotopic pancreatic tumors, with extended survival and ameliorated systemic toxicity. It is envisaged that the translation of cyclodiaryliodonium inhibitors with an optimized molecular design can be expedited by enzyme-activatable targeted delivery with improved pharmacokinetic profiles and preserved efficacy.
AIPH‐Encapsulated Thermo‐Sensitive Liposomes for Synergistic Microwave Ablation and Oxygen‐Independent Dynamic Therapy
Authors: Wenjie Zhang, Hu Zhou, Deyan Gong, Haitao Wu, Xiang Huang, Zhaohua Miao, Hu Peng, Zhengbao Zha
Journal: Advanced Healthcare Materials (2023)

Abstract Microwave ablation (MWA) is a novel treatment modality that can lead to the death of tumor cells by heating the ions and polar molecules in the tissue through high‐speed vibration and friction. However, the single hyperthermia is not sufficient to completely inhibit tumor growth. Herein, a thermodynamic cancer‐therapeutic modality has been fabricated which could be able to overcome hypoxia's limitations in the tumor microenvironment. Using thermo‐sensitive liposomes (TSLs) and oxygen‐independent radical generators (2,2’‐azobis[2‐(2‐imidazolin‐2‐yl)propane]dihydrochloride [AIPH]), a nano‐drug delivery system denoted as ATSL is developed for efficient sequential cancer treatment. Under the microwave field, the temperature rise of local tissue could not only lead to the damage of tumor cells but also induce the release of AIPH encapsulated in ATSL to produce free radicals, eliciting tumor cell death. In addition, the ATSL developed here would avoid the side effects caused by the uncontrolled diffusion of AIPH to normal tissues. The ATSLs have shown excellent therapeutic effects both in vitro and in vivo, suggesting its highly promising potential for clinic.